Field of the Invention
The present invention relates to a bacterium that induces the onset of diabetes and use thereof, as well as a detection method of the above bacterium and the like.
Discussion of the Background
Diabetes is a refractory disease that causes various complications since metabolic disorders including chronic hyperglycemia persist as a main pathology. Diabetes is classified based on the causal factor into type 1 diabetes, type 2 diabetes, diabetes due to genetic abnormality, diabetes associated with other disease or conditions, gestational diabetes and the like. Type 1 diabetes and type 2 diabetes are multi-factor disease developed by single nucleotide polymorphism (SNP), which is one of the genetic polymorphism rather than gene abnormality, added with various environmental factors. Type 1 diabetes is a diabetes developed when plural SNPs involved in autoimmunity and destruction of pancreatic β cells are added with environmental factors such as viral infection and the like to cause insulin deficiency resulting from the destructive lesion of pancreatic β cells (non-patent document 1). Type 2 diabetes is a diabetes developed when SNPs involved in insufficient insulin actions such as insulin secretion, insulin sensitivity and the like and SNPs involved in obesity are added with environmental factors such as overeating, high-fat diet, aging, smoking, lack of exercise and the like to cause abnormal signal transduction of insulin in adipose tissue, skeletal muscle and liver. Among the causal factors of type 2 diabetes, lowering of insulin sensitivity is dominant in Europeans and Americans, and lowering of insulin secretion capability of the pancreas also accompanies frequently in Japanese people (non-patent document 2).
While what causes the onset of diabetes is not completely clear, it is generally considered that type 2 diabetes is developed when people genetically prone to diabetes (genetic factor) acquire a lifestyle easily leading to diabetes (environmental factor).
As one of the environmental factors involved in the onset of diabetes, involvement of enteric bacteria has been clarified in recent years. In type 1 diabetes, it has been reported that the onset of diabetes in type 1 diabetes model rat was suppressed by drinking-water ingestion of a mixed aqueous solution of antibiotics including sulphamethoxazole, trimethoprime and colistine (non-patent document 3), and the symptoms of diabetes in type 1 diabetes model rat were mitigated by the administration of probiotics lactic acid bacterium Lactobacillus johnsonii N6.2 (non-patent document 4). There are more number of reports on the involvement of enteric bacteria in the onset of type 2 diabetes. Since increased insulin and inflammatory cytokine due to obesity act on the tight junction of the intestinal epithelial cells to increase paracellular permeability, and therefore, lipopolysaccharide (LPS), which is an enteric gram negative bacteria-derived cellular constituent component, can easily invade into the living organism. LPS taken into the portal vein is delivered to the liver, and recognized by Kupffer cell, which is a mononuclear cell in the liver, which triggers the release of inflammatory cytokine. As a result, insulin resistance of the liver is induced, and abnormal sugar metabolism and lipid metabolism are developed. Therefore, gluconeogenesis and glycogenolysis in the liver, which are intrinsically to be suppressed by insulin, are promoted to develop hyperglycemia. Also, LPS that invaded into the blood is similarly recognized by mononuclear cells such as macrophage and the like, which induces secretion of inflammatory cytokine, and decreases insulin sensitivity of skeletal muscles and adipose tissues. As a result, sugar uptake is suppressed and hyperglycemia is developed (reported in non-patent document 5).
In 2008, Cani et al. reported that administration of ampicillin and neomycin in drinking water to high-fat diet ingested mouse improves fasting blood glucose level, glucose tolerance, insulin resistance, and inflammation in adipose tissue (non-patent document 6). Furthermore, Membrez et al. reported in 2008 that administration of norfloxacin and ampicilin in drinking water to ob/ob mouse and high-fat diet ingested mouse significantly improves the fasting blood glucose level and glucose tolerance (non-patent document 7).
As for the type 2 diabetes improving effect of prebiotics, moreover, Cani et al. reported in 2007 and 2009 that the pathology of type 2 diabetes is improved by an increase in enteric bifidobacteria due to oligosaccharide (non-patent documents 8, 9).